journal article·2026-03Open access

GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer

Rodrigo Curvello, Sandra Hauser, Michael Seifert, Christopher K. Barlow, Joel R. Steele, Emma Salisbury, Daniel Croagh, Kathryn S. Stok, Anna V. Taubenberger, Ralf B. Schittenhelm, Daniela Loessner

Advanced Science· Volume 13· Issue 13

Abstract

ABSTRACT Pancreatic cancer cells rely on glutamine to sustain their survival in the stiff and poorly vascularized tumor microenvironment (TME). Inhibiting glutamic‐oxaloacetic transaminase 1 (GOT1) is a strategy to target glutamine metabolism and impair cancer cell functions. However, it remains unclear how cellular and extracellular elements of the TME respond to GOT1 inhibition. We engineered a pancreatic TME model ‘ on a dish ’ and recreated the metabolic interactions. Stromal cells remodeled the extracellular matrix and upregulated metabolic programs, including glutamine metabolism, oxidative phosphorylation, and central carbon metabolism. Cell responses to GOT1 inhibition were modulated by TME elements, with reductions in cell viability and proliferation occurring only under tissue‐like conditions. GOT1 inhibition altered matrix organization by upregulating different matrix‐related proteins, while it did not enhance cell responses to cytotoxic drugs. Our findings uncover the metabolic crosstalk within the TME and show that metabolism‐targeting treatments directly impact stromal elements of pancreatic cancer.
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Research context

OpenAlex topics: Cancer, Hypoxia, and Metabolism · Cancer Research and Treatments · Cancer Cells and Metastasis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Chemical and Biological Engineering, Faculty of Engineering Monash University Clayton Australia

Institute of Radiopharmaceutical Cancer Research Helmholtz‐Zentrum Dresden‐Rossendorf Department of Radiopharmaceutical and Chemical Biology Dresden Germany

Institute for Medical Informatics and Biometry (IMB), Faculty of Medicine Carl Gustav Carus Technische Universität Dresden Dresden Germany

Monash Proteomics and Metabolomics Platform Department of Biochemistry and Molecular Biology Biomedicine Discovery Institute Monash University Clayton Australia

Department of Upper GI and Hepatobiliary Surgery Monash Medical Centre Clayton Australia

Department of Surgery Monash University Clayton Australia

Department of Biomedical Engineering The University of Melbourne Parkville Australia

Biotechnology Center, Center for Molecular and Cellular Bioengineering Technische Universität Dresden Dresden Germany

Leibniz Institute of Polymer Research Dresden e.V. Max Bergmann Center of Biomaterials Dresden Germany

Department of Materials Science and Engineering, Faculty of Engineering Monash University Clayton Australia

Department of Anatomy and Developmental Biology Biomedicine Discovery Institute, Faculty of Medicine Nursing and Health Science Monash University Clayton Australia

Funding

National Health and Medical Research Council · HORIZON EUROPE Reforming and enhancing the European Research and Innovation system

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